Promoters and 3′ enhancers of human and mouse Epo genes, and schematic representation of the constructs.

(A) Nucleotide sequences of promoters and 3′ enhancers in mouse and human Epo genes, and the mutant fragments used in the present experiments. The upper sequences show the promoter regions that contain nuclear hormone receptor response element half-sites enclosed in solid lines. The mutations are shown either as base substitution (AATT) or deletion (■). The lower sequences show 3′ enhancers, where 3 important segments are enclosed in solid lines. The DR-2 element is an HNF-4 binding site in Hep3B cells. The mutations are shown either as base substitution (AAA and ATGCC) or deletion (○, ▵). (B) Schematic representation of the reporter gene constructs used. The upper construct shows the Luc reporter plasmids consisting of the mouse Epo promoter (mP) and 3′ enhancer (mE), and the lower construct shows the β-galactosidase reporter plasmid consisting of the human Epo promoter (hP) and 3′ enhancer (hE).